Taxol synthesis

Being a complex diterpenoid, the potent anticancer drug, Taxol, requires complicated steps for its biosynthesis. In the present article, recent advances on Taxol biosynthesis pathway are reviewed, including many recently reported genes that regulate Taxol biosynthesis. To meet the urgent need of clinic and scientific research, besides Taxus supply, other approaches to obtain Taxol have also been discussed here.Keywords: biosynthesis pathway, cell culture, endophytic fungi, Taxol, Taxu

Automatic Brain Tumor Segmentation using Convolutional Neural Networks with Test-Time Augmentation

Automatic brain tumor segmentation plays an important role for diagnosis, surgical planning and treatment assessment of brain tumors. Deep convolutional neural networks (CNNs) have been widely used for this task. Due to the relatively small data set for training, data augmentation at training time has been commonly used for better performance of CNNs. Recent works also demonstrated the usefulness of using augmentation at test time, in addition to training time, for achieving more robust predictions. We investigate how test-time augmentation can improve CNNs' performance for brain tumor segmentation. We used different underpinning network structures and augmented the image by 3D rotation, flipping, scaling and adding random noise at both training and test time. Experiments with BraTS 2018 training and validation set show that test-time augmentation helps to improve the brain tumor segmentation accuracy and obtain uncertainty estimation of the segmentation results.Comment: 12 pages, 3 figures, MICCAI BrainLes 201

Infection of a yellow baboon with simian immunodeficiency virus from African green monkeys:evidence for cross-species transmission in the wild

Many African primates are known to be naturally infected with simian immunodeficiency viruses (SIVs), but only a fraction of these viruses has been molecularly characterized. One primate species for which only serological evidence of SIV infection has been reported is the yellow baboon (Papio hamadryas cynocephalus). Two wild-living baboons with strong SIVAGM seroreactivity were previously identified in a Tanzanian national park where baboons and African green monkeys shared the same habitat (T. Kodama, D. P. Silva, M. D. Daniel, J. E. Phillips-Conroy, C. J. Jolly, J. Rogers, and R. C. Desrosiers, AIDS Res. Hum. Retroviruses 5:337-343, 1989). To determine the genetic identity of the viruses infecting these animals, we used PCR to examine SIV sequences directly in uncultured leukocyte DNA. Targeting two different, nonoverlapping genomic regions, we amplified and sequenced a 673-bp gag gene fragment and a 908-bp env gene fragment from one of the two baboons. Phylo-genetic analyses revealed that this baboon was infected with an SIVAGM strain of the vervet subtype. These results provide the first direct evidence for simian-to-simian cross-species transmission of SIV in the wild

The e-Index, Complementing the h-Index for Excess Citations

BACKGROUND: The h-index has already been used by major citation databases to evaluate the academic performance of individual scientists. Although effective and simple, the h-index suffers from some drawbacks that limit its use in accurately and fairly comparing the scientific output of different researchers. These drawbacks include information loss and low resolution: the former refers to the fact that in addition to h(2) citations for papers in the h-core, excess citations are completely ignored, whereas the latter means that it is common for a group of researchers to have an identical h-index. METHODOLOGY/PRINCIPAL FINDINGS: To solve these problems, I here propose the e-index, where e(2) represents the ignored excess citations, in addition to the h(2) citations for h-core papers. Citation information can be completely depicted by using the h-index together with the e-index, which are independent of each other. Some other h-type indices, such as a and R, are h-dependent, have information redundancy with h, and therefore, when used together with h, mask the real differences in excess citations of different researchers. CONCLUSIONS/SIGNIFICANCE: Although simple, the e-index is a necessary h-index complement, especially for evaluating highly cited scientists or for precisely comparing the scientific output of a group of scientists having an identical h-index

New Alzheimer Amyloid β Responsive Genes Identified in Human Neuroblastoma Cells by Hierarchical Clustering

Alzheimer's disease (AD) is characterized by neuronal degeneration and cell loss. Aβ42, in contrast to Aβ40, is thought to be the pathogenic form triggering the pathological cascade in AD. In order to unravel overall gene regulation we monitored the transcriptomic responses to increased or decreased Aβ40 and Aβ42 levels, generated and derived from its precursor C99 (C-terminal fragment of APP comprising 99 amino acids) in human neuroblastoma cells. We identified fourteen differentially expressed transcripts by hierarchical clustering and discussed their involvement in AD. These fourteen transcripts were grouped into two main clusters each showing distinct differential expression patterns depending on Aβ40 and Aβ42 levels. Among these transcripts we discovered an unexpected inverse and strong differential expression of neurogenin 2 (NEUROG2) and KIAA0125 in all examined cell clones. C99-overexpression had a similar effect on NEUROG2 and KIAA0125 expression as a decreased Aβ42/Aβ40 ratio. Importantly however, an increased Aβ42/Aβ40 ratio, which is typical of AD, had an inverse expression pattern of NEUROG2 and KIAA0125: An increased Aβ42/Aβ40 ratio up-regulated NEUROG2, but down-regulated KIAA0125, whereas the opposite regulation pattern was observed for a decreased Aβ42/Aβ40 ratio. We discuss the possibilities that the so far uncharacterized KIAA0125 might be a counter player of NEUROG2 and that KIAA0125 could be involved in neurogenesis, due to the involvement of NEUROG2 in developmental neural processes

Infective endocarditis caused by methicillin-resistant Staphylococcus aureus in a young woman after ear piercing: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ear piercing is a common practice among Korean adolescents and young women and usually is performed by nonmedical personnel, sometimes under suboptimal hygienic conditions. Consequently, ear piercing has been associated with various infectious complications, including fatal infective endocarditis. We report a case of infective endocarditis that was caused by community-associated methicillin-resistant <it>Staphylococcus aureus </it>after ear piercing and that was accompanied by a noticeable facial rash.</p> <p>Case presentation</p> <p>A 29-year-old Korean woman underwent ear piercing six days before hospitalization. On admission, she had fever, erythematous maculopapular rashes on her face, signs of generalized emboli, vegetation in her mitral valve, and methicillin-resistant <it>S. aureus </it>bacteremia. On the basis of the blood culture results, she was treated with vancomycin in combination with gentamicin. On day six of hospitalization, a rupture of the papillary muscle of her mitral valve developed, and emergency cardiac surgery replacing her mitral valve with a prosthetic valve was performed. After eight weeks of antibiotic therapy, she was treated successfully and discharged without significant sequelae.</p> <p>Conclusions</p> <p>Numerable cases of body piercing-related infective endocarditis have been reported, and since ear piercing is commonplace nowadays, the importance of risk recognition cannot be overemphasized. In our report, a patient developed infective endocarditis that was caused by methicillin-resistant <it>S. aureus </it>after ear piercing and that was accompanied by an interesting feature, namely facial rash.</p

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD)

<p>Abstract</p> <p>Background</p> <p>Although polymorphisms of <it>PRNP</it>, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s) modulating susceptibility to prion disease. Ribosomal protein SA (<it>RPSA</it>), also called 37 kDa laminin receptor precursor (LRP)/67 kDa laminin receptor (LR), acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR.</p> <p>Methods</p> <p>To identify other susceptibility genes involved in prion disease, we performed genetic analysis of <it>RPSA</it>. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD) patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on <it>RPSA </it>by direct sequencing or restriction fragment length polymorphism (RFLP) analysis.</p> <p>Results</p> <p>We observed four single nucleotide polymorphisms (SNPs), including -8T>C (rs1803893) in the 5'-untranslated region (UTR) of exon 2, 134-32C>T (rs3772138) in the intron, 519G>A (rs2269350) in the intron and 793+58C>T (rs2723) in the intron on the <it>RPSA</it>. The 519G>A (at codon 173) is located in the direct PrP binding site. The genotypes and allele frequencies of the <it>RPSA </it>polymorphisms showed no significant differences between the controls and sporadic CJD patients.</p> <p>Conclusion</p> <p>These results suggest that these <it>RPSA </it>polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of <it>RPSA </it>gene with sporadic CJD.</p